Differentiation and encapsulation of β-like cells in cell therapy for the treatment of type 1 diabetes

  • Camille ROLIN

Student thesis: Master typesMaster in Biomedecine, professional focus in preclinical research


Background: Type 1 diabetes mellitus is an auto-immune disease causing the T-cell mediated destruction of insulin-producing β-cells, resulting in chronic hyperglycemia. The current treatments consist mostly in insulin replacement therapy, presenting a major burden for the patient, and in some cases in pancreas or pancreatic islets transplantation, limited by the donor shortage and the need for life-long immunosuppressive treatments. The encapsulation of stem cell-derived β-cells in a semi-permeable membrane with selective diffusion properties could offer a sustainable solution to overcome these limitations.

Aim: The main goals of this master thesis were to optimize the differentiation process of human induced pluripotent stem cells towards a β-like cell phenotype, as well as to develop a biocompatible encapsulation material maintaining cell viability and metabolic activity.

Methods: To optimize the differentiation programme, two hiPSC-lines (AICS-0011 and HEL 115.6) were used. The cell morphology as well as the expression of several key gene markers were monitored at crucial stages of the differentiation programme. To optimize the biocompatibility of the matrix towards the encapsulated cells, INS-1E cells were encapsulated by a one-step in situ sol-gel process and the effect on cell viability and the oxygen consumption rate was analyzed over time. Furthermore, the porosity and diffusion properties of the matrix were studied by nitrogen physisorption analyses and by assessing the response of encapsulated cells to IL-1β and TNF-α.

Results: AICS-0011 cells display a limited potential for an efficient pancreatic differentiation, while better results were obtained with HEL 115.6 cells which exhibit promising modifications of their morphology and genetic expression profile during the differentiation programme. Regarding the biocompatibility of the matrix, INS-1E cells present a higher sensitivity to the encapsulation stress than other tested cell lines, as evidenced by a strong decrease in cell viability and the decrease in oxygen consumption rate 1 or 3 day(s) post-encapsulation. Finally, the analysis of the porosity and diffusion properties seemed to indicate that the matrix is permeable to IL-1β.

Conclusion: According to the results focusing on the first 12 days of cell differentiation, HEL 115.6 cells seem to exhibit a good potential for the pancreatic differentiation. The analyses concerning the biocompatibility of the matrix have revealed that INS-1E cells might not represent the best cell model, or at least that the matrix and encapsulation process are not appropriate for these cells. The nitrogen physisorption analyses have indicated that the modulation of the chemical composition and incubation times affect the porosity and might be used to prevent the diffusion of pro-inflammatory cytokines.
Date of Award19 Jan 2021
Original languageEnglish
Awarding Institution
  • University of Namur
SupervisorThierry Arnould (Supervisor)


  • diabetes
  • β-cells
  • hiPSC
  • differentiation
  • encapsulation

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